数字农科院2.0

Uterine macrophages as treatment targets for therapy of premature rupture of membranes by modified ADSC-EVs through a circRNA/miRNA/NF-κB pathway

文献类型： 外文期刊

作者： Yuhua Gao;Ningning Mi;Ying Zhang;Xiangchen Li;Weijun Guan;Chunyu Bai

作者机构：

关键词： ADSCs;Extracellular vesicles;Macrophages;MMPs;PROM

期刊名称： Journal of Nanobiotechnology

ISSN： 1477-3155

年卷期： 2022 年 20 卷 1 期

页码：

收录情况： SCIE（2022版） ; ; EI（2022版）

摘要： Background: Circular RNA (circRNA) is a type of stable non-coding RNA that modifies macrophage inflammation by sponging micro RNAs (miRNAs), binding to RNA-binding proteins, and undergoing translation into peptides. Activated M1 phenotype macrophages secrete matrix metalloproteinases to participate in softening of the cervix uteri to promote vaginal delivery. Methods: In this study, the premature rupture of membranes (PROM) mouse model was used to analyze the role of macrophages in this process. Profiling of circRNAs was performed using a competing endogenous RNA microarray, and their functions were elucidated in vitro. Meanwhile, adipose tissue-derived stem cell-secreted extracellular vesicles (EVs) were applied as a vehicle to transport small interfering RNAs (siRNAs) targeting the circRNAs to demonstrate their biological function in vivo. Results: The miRNA miR-1931 is dependent on the nuclear factor kappa-B (NF-κB) pathway but negatively regulates its activation by targeting the NF-κB signaling transducer TRAF6 to prevent polarization of M1 macrophages and inhibit matrix metalloproteinase (MMP) secretion. The host gene of circRNA B4GALNT1, also an NF-κB pathway-dependent gene, circularizes to form circRNA_0002047, which sponges miR-1931 to maintain NF-κB pathway activation and MMP secretion in vitro. In the PROM model, EVs loaded with siRNAs targeting circRNAs demonstrated that the circRNAs reduced miR-1931 expression to maintain NF-κB pathway activation and MMP secretion for accelerating PROM in vivo. Conclusions: Our data provide insights into understanding PROM pathogenesis and improving PROM treatment.

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